成纤维细胞生长因子 23 和 Klotho 与 CKD 2-4 期患者心血管结局的关系。
Associations of FGF-23 and sKlotho with cardiovascular outcomes among patients with CKD stages 2-4.
机构信息
Department of Internal Medicine IV-Nephrology and Hypertension, Saarland University Medical Centre, Homburg, Germany;
Labor Dr Limbach und Kollegen, Medizinisches Versorgungszentrum, Heidelberg, Germany; and.
出版信息
Clin J Am Soc Nephrol. 2014 Jun 6;9(6):1049-58. doi: 10.2215/CJN.07870713. Epub 2014 Mar 27.
BACKGROUND AND OBJECTIVES
CKD-mineral and bone disorders (CKD-MBD) measures contribute to cardiovascular morbidity in patients with CKD. Among these, fibroblast growth factor (FGF)-23 and its coreceptor Klotho may exert direct effects on vascular and myocardial tissues. Klotho exists in a membrane-bound and a soluble form (sKlotho). Recent experimental evidence suggests sKlotho has vasculoprotective functions.
DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: Traditional and novel CKD-MBD variables were measured among 444 patients with CKD stages 2-4 recruited between September 2008 and November 2012 into the ongoing CARE FOR HOMe study. Across tertiles of baseline sKlotho and FGF-23, the incidence of two distinct combined end points was analyzed: (1) the first occurrence of an atherosclerotic event or death from any cause and (2) the time until hospital admission for decompensated heart failure or death from any cause.
RESULTS
Patients were followed for 2.6 (interquartile range, 1.4-3.6) years. sKlotho tertiles predicted neither atherosclerotic events/death (fully adjusted Cox regression analysis: hazard ratio [HR] for third versus first sKlotho tertile, 0.75 [95% confidence interval (95% CI), 0.43-1.30]; P=0.30) nor the occurrence of decompensated heart failure/death (HR for third versus first sKlotho tertile, 0.81 [95% CI, 0.39-1.66]; P=0.56). In contrast, patients in the highest FGF-23 tertile had higher risk for both end points in univariate analysis. Adjustment for kidney function attenuated the association between FGF-23 and atherosclerotic events/death (HR for third versus first FGF-23 tertile, 1.23 [95% CI, 0.58-2.61]; P=0.59), whereas the association between FGF-23 and decompensated heart failure/death remained significant after adjustment for confounders (HR for third versus first FGF-23 tertile, 4.51 [95% CI, 1.33-15.21]; P=0.02).
CONCLUSIONS
In this prospective observational study of limited sample size, sKlotho was not significantly related to cardiovascular outcomes. FGF-23 was significantly associated with future decompensated heart failure but not incident atherosclerotic events.
背景和目的
慢性肾脏病-矿物质和骨异常（CKD-MBD）的指标会导致 CKD 患者的心血管发病率升高。在这些指标中，成纤维细胞生长因子 23（FGF-23）及其核心受体 Klotho 可能对血管和心肌组织产生直接影响。Klotho 存在于膜结合形式和可溶性形式（sKlotho）。最近的实验证据表明，sKlotho 具有血管保护功能。
设计、设置、参与者和测量：在 2008 年 9 月至 2012 年 11 月期间招募的 444 名 CKD 2-4 期患者中，测量了传统和新型 CKD-MBD 变量，这些患者均被纳入正在进行的 CARE FOR HOMe 研究。根据基线 sKlotho 和 FGF-23 的三分位数，分析了两个不同的复合终点的发生率：（1）首次发生动脉粥样硬化事件或任何原因导致的死亡；（2）因失代偿性心力衰竭或任何原因导致住院的时间。
结果
患者的中位随访时间为 2.6 年（四分位距，1.4-3.6 年）。sKlotho 三分位数既不能预测动脉粥样硬化事件/死亡（完全调整的 Cox 回归分析：第 3 与第 1 sKlotho 三分位数的风险比[HR]，0.75 [95%置信区间（95%CI），0.43-1.30]；P=0.30），也不能预测失代偿性心力衰竭/死亡（第 3 与第 1 sKlotho 三分位数的 HR，0.81 [95%CI，0.39-1.66]；P=0.56）。相反，在单变量分析中，最高 FGF-23 三分位数的患者发生这两个终点的风险更高。调整肾功能后，FGF-23 与动脉粥样硬化事件/死亡之间的关联减弱（第 3 与第 1 FGF-23 三分位数的 HR，1.23 [95%CI，0.58-2.61]；P=0.59），而 FGF-23 与失代偿性心力衰竭/死亡之间的关联在调整混杂因素后仍具有统计学意义（第 3 与第 1 FGF-23 三分位数的 HR，4.51 [95%CI，1.33-15.21]；P=0.02）。
结论
在这项样本量有限的前瞻性观察性研究中，sKlotho 与心血管结局无显著相关性。FGF-23 与未来失代偿性心力衰竭显著相关，但与动脉粥样硬化事件无关。
Zotero 插件